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dc.contributor.authorKänsäkoski Johanna
dc.contributor.authorJääskeläinen Jarmo
dc.contributor.authorJääskeläinen Tiina
dc.contributor.authorTommiska Johanna
dc.contributor.authorSaarinen Lilli
dc.contributor.authorLehtonen Rainer
dc.contributor.authorHautaniemi Sampsa
dc.contributor.authorFrilander Mikko J
dc.contributor.authorPalvimo Jorma J
dc.contributor.authorToppari Jorma
dc.contributor.authorRaivio Taneli
dc.date.accessioned2017-03-02T11:48:33Z
dc.date.available2017-03-02T11:48:33Z
dc.date.issued2016
dc.identifier10.1038/srep32819fi_FI
dc.identifier.issn2045-2322
dc.identifier.urihttps://erepo.uef.fi/handle/123456789/404
dc.descriptionArticle
dc.description.abstractMutations in the X-linked androgen receptor (AR) gene underlie complete androgen insensitivity syndrome (CAIS), the most common cause of 46,XY sex reversal. Molecular genetic diagnosis of CAIS, however, remains uncertain in patients who show normal coding region of AR. Here, we describe a novel mechanism of AR disruption leading to CAIS in two 46,XY sisters. We analyzed whole-genome sequencing data of the patients for pathogenic variants outside the AR coding region. Patient fibroblasts from the genital area were used for AR cDNA analysis and protein quantification. Analysis of the cDNA revealed aberrant splicing of the mRNA caused by a deep intronic mutation (c.2450-118A>G) in the intron 6 of AR. The mutation creates a de novo 5′ splice site and a putative exonic splicing enhancer motif, which leads to the preferential formation of two aberrantly spliced mRNAs (predicted to include a premature stop codon). Patient fibroblasts contained no detectable AR protein. Our results show that patients with CAIS and normal AR coding region need to be examined for deep intronic mutations that can lead to pseudoexon activation.fi_FI
dc.language.isoENfi_FI
dc.publisherNature Publishing Groupfi_FI
dc.relation.ispartofseriesScientific Reports
dc.relation.urihttp://doi.org/10.1038/srep32819fi_FI
dc.rightsCC BY http://creativecommons.org/licenses/by/4.0/fi_FI
dc.subjectEndocrine reproductive disordersfi_FI
dc.subjectMedical geneticsfi_FI
dc.titleComplete androgen insensitivity syndrome caused by a deep intronic pseudoexon-activating mutation in the androgen receptor genefi_FI
dc.typehttp://purl.org/eprint/type/JournalArticle
dc.description.versionPublisher's pdffi_FI
dc.contributor.departmentSchool of Medicine / Biomedicine
dc.contributor.departmentSchool of Medicine / Dentistry,School of Medicine / Clinical Medicine
uef.solecris.id42710274
eprint.statushttp://purl.org/eprint/status/PeerReviewedfi_FI
dc.type.publicationinfo:eu-repo/semantics/article
dc.rights.accessrights© The Authorsfi_FI
dc.relation.doi10.1038/srep32819
dc.description.reviewstatushttp://purl.org/eprint/status/PeerReviewed
dc.relation.articlenumber32819
dc.relation.issn2045-2322
dc.relation.volume6


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